The present invention relates to a combination of active substances for enhancing the skin""s defense against chemical and physical irritations, for example, from job-related stress, strain on the skin from leisure activities (bathing, showering, sun exposure, household chemicals, building materials, etc.) and from the working environment.
A large number of skin protection agents has been used for skin protection for decades, without any experimental evidence of their effectiveness. Usually, skin protection is achieved by an exposure barrier, sometimes in connection with an increase of skin moisture, rather than by enhancement of the barrier function and the defense of the skin against irritations by biochemical means (Elsner P., Wigger-Alberti W. (1997), Der Hautschutz in der Prxc3xa4vention der Berufsdermatosen, Dt. xc3x84rzteblatt 94; 17-1489-A-1492).
For the active substance rhodanide (thiocyanate), a number of applications involving biological effects on the cutaneous system have been established experimentally. Kramer A.: Prxc3xcf-system zur Erfassung der Vertrxc3xa4glichkeit antimikrobiell wirksamer Stoffe und Zubereitungen zur episomatischen Applikation durch in-vitro- und tierexperimentelle Tests (Episomatiktest) und toxikohygienische Bewertung als Bestandteil krankenhaushygienischer Aufgabenstellungen; Diss. B. Med. Fak. Univ. Greifwald (1985), describes the accelerated closing of skin wounds. DE 41 34 888 A describes the accelerated healing of UV-induced erythema (sunburn).
A. Kramer, W. Weuffen, S. Minnich, S. Koch, M. Minnich, H. Below, B. Thxc3xcrkow and H. Meffert (1990), Fxc3x6rderung der Haarentwicklung durch Thiocyanat beim Meerschweinchen; Dermatol. Mschr. 176: 417-420, describe the growth enhancement of integumentary appendage (hair).
Also for the active substance urea, a number of effects have been known, i.e., the following (Wohlrab W. (1989), Bedeutung von Harnstoff in der externen Therapie, Hautarzt 40, Suppl. 9: 35-41), the respective application ranges for the following effects of urea not remaining under 2% by weight: hydration of the Stratum corneum, keratolytic properties, acceleration of penetration, inhibition of epidermal proliferation (basal cells), a small extent of antimicrobial activity, antipruriginous effect, proteo- and mucolytical activities and buffering effect (regulation of the hydrolipid coat).
The following therapeutically useful effects result from these properties of urea (Raab W. (1989), Biochemie, Pharmakologie und Toxikologie von Harnstoff; Hautarzt 40, Suppl. 9: 23-26): hydration of the Stratum corneum, keratolysis of diseased nails, desquamation, reduction of excessive cell divisions, alleviation of itching, saving of preservatives from antimicro-bial effect and improvement of the penetration of incorporated pharmaceuticals.
In modern dermatotherapy, urea is successfully employed as a single drug or as an additive in the healing phase of dermatoses. As a single drug, urea is employed for eczemas of dry skin, for desquamative lesions, for hyperkeratoses and for many other chronical dermatoses (Swanbeck G. (1989), Harnstoff als Monotherapeutikum bei trockener Haut; Hautarzt 40, Suppl. 9: 42-43). In topical dermatological preparations, urea is often combined with glucocorticoids (Drosner M. (1989), Harnstoff in Kombination mit Kortikosteroiden zur Therapie von Ekzemen; Hautarzt 40, Suppl. 9: 47-50), with dithranol (Przybilla B., Kaudewitz P., Biber K. (1989), Harnstoff in Kombination mit Dithranol zur Therapie der Psoriasis vulgaris; Hautarzt 40, Suppl. 9: 54-57), with tretinoin (Mxc3xcller K. H., Pflugshaupt Ch. (1989); Harnstoff in der Dermatologie; Hautarzt 40, Suppl. 9:16), and with salicylic acid (Gabard B., Bieli E. (1989); Salicylsxc3xa4ure und Harnstoffxe2x80x94mxc3x6gliche Beeinflussung der keratolytischen Wirkung von Salicylsxc3xa4ure durch Harnstoff; Hautarzt 40, Suppl. 9: 71-73). For neurodermitis, Psoriasis vulgaris and disturbed hornification (Raab, supra), the regular application of urea-containing topical preparations is recommended for the rehabilitation of the skin and for the prophylaxis of skin lesions, as well as for dry-lipopenic skin condition. As cannot be expected otherwise, from its physiological occurrence in the organism (Hibber J. M., Jackson A. A. (1991); Variation in measures of urea kinetics over four years in a single adult; Europ. J. Clin. Nutr. 45: 347-351), urea is well tolerated epidermally. A sensitizing potency or other side-effects of urea have not been detected (Ashton H., Frenk E., Stevenson C. J. (1971); Urea as a topical agent; Brit. J. Derm. 84: 194-196; Wozniak K. D. (1975); Hauttestungen verschiedener Harnstofftypen; Derm. Mschr. 161: 687).
U.S. Pat. No. 3,384,548 employs urea (from 2 to 7.5% by weight) and thiocyanate ions (4% by weight) as a swelling agent for the depilation of hair.
DE 43 41 001 A1 mentions a urea content of from 0.1 to 10% by weight for moisture absorption.
However, an anti-irritative activity in a narrower sense has not been known for urea and cannot be derived from the available results.
It has been the object of the invention to provide novel effective agents for the prophylaxis of skin lesions, achieved through a physiological skin protective activity using biochemical means, with the simultaneous stimulation of healing and repair processes, so that the overall effect is a revitalizing skin protection.
This object has been achieved by a combination of ionically bound and/or free thiocyanate ions with urea in addition to per se known carriers and auxiliary agents. Both thiocyanate and urea are physiological substrates which occur in various compartments in the human organism; according to the invention, they are employed within a physiological concentration range in the combination of active substances.
The surprising property of this combination of active substances is the fact that, if their application precedes an irritation, they significantly suppress the manifestation of such irritation, in contrast to known antiphlogistics, which can only affect diseased tissues. Such a mode of action has not been known to date.
It is particularly preferred according to the present invention that the thiocyanate ions are in the form of alkali metal salts including ammonium salts and their derivatives. Thus, these are ionizable thiocyanates as opposed to covalently bound organic thiocyanates. It is particularly preferred according to the present invention that the alkali metal salts of said thiocyanates are selected from sodium, potassium and ammonium thiocyanates.
According to the present invention, it is particularly preferred that the agents contain from 0.01% to 1% by weight of thiocyanate ions and from 0.1% to 10% by weight, especially upto 1% by weight, of urea. In addition to the active ingredients thiocyanate and urea, the agents according to the invention contain usual auxiliary agents and carriers for ointments, creams, emulsions or lotions of w/o and o/w types or aqueous solutions.
They are known, for example, from H. P. Fiedler, Lexikon der Hilfsstoffe fxc3xcr Pharmazie, Kosmetik und angewandte Gebiete, 4th edition (1996), and according to the invention, they are not to alter or at least not to adversely affect the behavior of active substances applied to the skin. The same applies to the carriers. According to the present invention, it is particularly preferred that the weight ratio of thiocyanate ions to urea is from 1:10 to 1:50.
According to the present invention, the term xe2x80x9cureaxe2x80x9d is used to include per se known urea derivatives, such as monoacetylurea.
On the basis of additive combination effects, the combination of thiocyanate and urea according to the invention resulted in the surprising skin protective effect of the combination of substances against noxious agents or the above mentioned stresses, the known effect of thiocyanate having been surprisingly improved by combining it with urea. With the present invention, the possibility of an extensive mode of action of a revitalizing skin protection has been realized.
One particular embodiment of the invention is the use of the above defined agents for enhancing the skin""s defenses against chemical and physical irritations, especially from job-related stress, strain on the skin from leisure activities and from the working environment. Thus, the combination of active substances according to the invention serves, in particular, for the preventive protection against aggressive media in the workaday routine as well as in the handling of protective media against external influences on the skin.